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DETERMINE Trial Treatment Arm 02: Atezolizumab in Adult, Paediatric and Teenage/Young Adult Patients With Cancers With High Tumour Mutational Burden (TMB) or Microsatellite Instability-high (MSI-high) or Proven Constitutional Mismatch Repair Deficiency (CMMRD) Disposition

RecruitingPhase 2, Phase 3Ages any - anyAllCancer Research UK
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In plain words

What the trial is, and whether it could suit you

This clinical trial is looking at a drug called atezolizumab. Atezolizumab is approved as standard of care treatment for adult patients with urothelial cancer, non-small cell lung cancer, extensive-stage small cell lung cancer, hepatocellular carcinoma and triple negative breast cancer. This means it has gone through clinical trials and been approved by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. Atezolizumab works in patients with these types of cancers which have certain changes in the cancer cells called high tumour mutational burden (TMB) or high microsatellite instability (MSI) or proven (previously diagnosed) constitutional mismatch repair deficiency (CMMRD). Investigators now wish to find out if it will be useful in treating patients with other cancer types which are also TMB/MSH-high or show CMMRD. If the results are positive, the study team will w

Sign in to get the eligibility rules as simple questions to take to your doctor.

๐Ÿ“‹ Eligibility rules (as published)
THE PATIENT MUST FULFIL THE ELIGIBILITY CRITERIA WITHIN THE DETERMINE MASTER PROTOCOL (NCT05722886) AND WITHIN THE TREATMENT ARM 02 (ATEZOLIZUMAB) OUTLINED BELOW\* \*When atezolizumab-specific inclusion/exclusion criteria or precautions below differ from those specified in the Master Protocol, the atezolizumab-specific criteria will take precedence. Inclusion Criteria: A. Confirmed diagnosis of a malignancy that is high TMB (defined as โ‰ฅ10 mut/Mb), MSI-high or of proven (previously diagnosed) CMMRD disposition using an analytically validated next-generation sequencing method. Patient cases with TMB between 10-15 mut/Mb may be discussed in an MTB meeting. TMB โ‰ฅ19 mut/Mb will be fast-tracked for an MTB recommendation, unless there are any patient-specific individualities (such as multiple gene amplifications) that require MTB discussion. B. Women of childbearing potential are eligible provide they meet the following criteria: * Have a negative serum or urine pregnancy test before enrolment and; * Agree to use one form of effective birth control method such as: I. combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (\[oral, intravaginal or transdermal\]); II. progestogen-only hormonal contraception associated with or without inhibition of ovulation (oral, injectable or implantable); III. intrauterine device (IUD), IV. intrauterine hormone-releasing system (IUS), V. bilateral tubal occlusion, VI. vasectomised partner, VII. sexual abstinence, VIII. male or female condom with or without spermicide; IX. cap, diaphragm or sponge with spermicide. Effective from the first administration of atezolizumab, throughout the trial and for five months after the last administration of atezolizumab. C. Male patients with partners who are women of childbearing potential are eligible provided that they agree to the following, from the first administration of atezolizumab, throughout the trial until the last administration of atezolizumab: * Agree to take measures not to father children by using a barrier method of contraception (condom plus spermicide) or sexual abstinence. * Non-vasectomised male patients with partners who are women of childbearing potential must also be willing to ensure that their partner uses an effective method of contraception. * Male patients with pregnant or lactating partners must be advised to use barrier method contraception (e.g. condom) to prevent drug exposure of the foetus or neonate. All male patients must refrain from donating sperm for the same period. D. Patients must be able and willing to undergo a fresh tissue biopsy at baseline and blood samples for translational research. Note that for patients with haematological malignancies or neuroblastomas, blood, bone marrow aspiration and/or trephine or lymph node biopsy samples may be taken. E. ADULT PATIENTS (โ‰ฅ18 years): Adequate organ function as per haematological and biochemical indices within the ranges defined in the protocol. These measurements should be performed to confirm the patient's eligibility. F. PAEDIATRIC PATIENTS (\<18 years): Adequate organ function as per haematological and biochemical indices within the ranges defined in the protocol. These measurements should be performed to confirm the patient's eligibility. G. Patients must have stable thyroid function tests. Patients on stable doses of thyroxine replacement are permitted. Exclusion Criteria: A. Diagnosis of urothelial cancer, non-small cell lung cancer, extensive-stage small cell lung cancer, hepatocellular carcinoma or triple negative breast cancer. B. Patients with rapidly progressing or symptomatically deteriorating brain metastases and/or leptomeningeal disease. Patients with previously treated brain metastases are eligible, provided the patient has not experienced a seizure or had a clinically significant change in neurological status within 14 days (for adult patients) or 7 days (for paediatric patients) prior to the start of IMP administration. Such patients must be non-dependent on steroids or on a stable or reducing dose of steroid treatment for at least 14 days (or 7 days for paediatric patients) prior to the start of IMP administration. Primary brain or central nervous system (CNS) malignancies are allowed providing the patient is clinically stable (if requiring corticosteroids must be at stable or decreasing doses for at least 14 days for adults and 7 days for paediatric patients prior to the start of IMP administration). Patients who have received brain irradiation must have completed whole-brain radiotherapy and/or stereotactic radiosurgery at least 14 days prior to the start of IMP administration. โ€ข Paediatric patients with either primary brain tumours or extracranial solid tumours with intracranial metastases with one or more intracranial lesions should only be considered for inclusion if largest intracranial lesion is โ‰ค6 cm in longest axis. Consideration should also be given to the intracranial location of the tumour and potential risk should swelling occur. This is because of the class risk of immune checkpoint inhibitors such as atezolizumab causing immune-mediated inflammatory response and 'tumour flare' which may result in acute neurological deterioration. C. Female patients who are pregnant, breastfeeding or planning to become pregnant during the trial or within five months following their last dose of atezolizumab. D. History or clinical evidence of current inflammatory lung disease: * History of idiopathic pulmonary fibrosis, organising pneumonia (e.g. bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis. * Evidence of active pneumonitis on screening chest computed tomography (CT) scan. E. Active autoimmune disease that requires the use of systemic immunomodulatory therapy (i.e. with disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy for hypothyroidism and adrenal or pituitary
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What it tests

  • Atezolizumab
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Where

27 sites
Belfast City Hospital
Belfast, United Kingdom
University Hospital Birmingham
Birmingham, United Kingdom
Birmingham Children's Hospital
Birmingham, United Kingdom
Bristol Royal Hospital for Children
Bristol, United Kingdom
Bristol Haematology and Oncology Centre
Bristol, United Kingdom
Addenbrooke's Hospital
Cambridge, United Kingdom
Velindre Cancer Centre
Cardiff, United Kingdom
Cardiff Children's Hospital
Cardiff, United Kingdom

โ€ฆand 19 more on ClinicalTrials.gov.

๐Ÿค Taking part is your choice, and you can leave at any time. Only the trial team can confirm you are eligible โ€” always decide together with your own doctor.
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